A folic acid conjugated polyethylenimine-modified PEGylated nanographene loaded photosensitizer: photodynamic therapy and toxicity studies in vitro and in vivo

Abstract

Targeted cancer therapies are currently a strong focus in biomedical research. Our recent studies have demonstrated that polyethylenimine-modified PEGylated nanographene loaded chlorin e6 (PPG–Ce6) shows excellent photodynamic efficacy because of the significantly enhanced intracellular targeted delivery of Ce6 to lysosomes. Based on our previous research, in this work, a novel nanographene-based tumor targeting delivery system was developed to selectively transport the photosensitizer into the tumor cells. In brief, we describe that the folic acid (FA) conjugated polyethylenimine-modified PEGylated nanographene system (PPG–FA) delivered in a targeted manner chlorin e6 (Ce6) to the tumor to simultaneously achieve targeted photodynamic therapy and biological imaging. The cellular internalization and the cellular uptake of PPG–FA–Ce6 were assessed, which indicated that the intracellular uptake of PPG–FA–Ce6 was target-specific. In vitro and in vivo photodynamic therapy results showed that PPG–FA–Ce6 exhibits excellent targeted delivery of Ce6, leading to simultaneous significant targeted photodynamic therapy and imaging. More importantly, the toxicity studies showed that PPG–FA–Ce6 had low toxicity as evidenced by blood biochemistry, hematological analysis, and histological examination. Our present work demonstrates that PPG–FA–Ce6 has high photodynamic therapy efficacy with no obvious toxicity because of its good tumor targeting property which can be potentially utilized in the biomedicine field.